Centre for Functional Genomics and Human Disease

Inflammation and Immunity

Interferons are natural substances produced by the body in response to infection and disease. Their main function is to "interfere" with viral growth and so stop the spread of a virus. Since their discovery 43 years ago scientists have found that Interferons have other functions such as stimulating the immune system and also stopping tumour cells from growing.

Manufactured forms of Interferon have been shown to help the body's immune system fight diseases like cancer and viral infections more effectively. Interferon can be injected into a vein, into a muscle, or under the skin or taken orally. Daily injection under the skin is the most common method of treatment.

Interferon is currently used for treating diseases such as:

* Multiple Sclerosis
* Hepatitis B and C
* Melanoma
* Hairy cell leukemia
* Non-Hodgkins Lymphoma
* Genital Warts
* AIDS-related Kaposi's sarcoma

Patients with these diseases are significantly more likely to get better than those untreated. However, some patients who are given Interferon therapy experience many unpleasant side-effects such as flu-like symptoms and some of these patients do not even get better after their treatment.

Ideally doctors want to be able to identify those patients who are most likely to respond to Interferon treatment and spare those patients who are unlikely to benefit from any of the unpleasant side effects.

We have recently discovered a protein, the soluble IFN receptor, that normally circulates in the blood and acts as a natural "brake" to the actions of IFNs by combining with IFN. Some individuals have high levels of this protein and so the beneficial effects of IFN might be completely blocked or at least greatly reduced because the soluble IFN receptor might interfere with injected IFN.

In Down Syndrome there are three copies of human chromosome 21. The gene for the soluble IFN receptor is located on this chromosome. Individuals with Down Syndrome are more likely to succumb to viral infections and have many problems with their immune systems compared to the general population. It is possible that these defects could be caused by excess levels of soluble IFN receptor blocking the normal effects of IFNs.

It is essential that we understand how IFN production and action are regulated so that benefits to the patient outweigh the adverse effects.

The results of our research will improve the therapeutic potential and maximise the clinical efficacy of IFNs.

We are studying Interferons with the following techniques:

* Use of mouse models such as transgenic and knockout mice to try and mimic different disease situations in humans
* Microarray technology
* Development of a blood test so that we can screen patients who have high levels of soluble IFN receptor. These patients could be then spared a treatment that might cause them discomfort and may not even work